NF2 Mutations in Secretory and Other Rare Variants of Meningiomas

Abstract

The WHO classification defines different histological variants of meningiomas. Mutations of the tumor suppressor gene NF2 on 22q have been described in 30% to 60 % of sporadic meningiomas. However, the vast majority of the meningiomas that have been subject to NF2 analysis belong to the most frequent variants like transitional, fibroblastic and meningothelial meningiomas. Within these subtypes, transitional and fibroblastic meningiomas harbor significantly more NF2 mutations than meningothelial meningiomas, indicating molecular subsets of these tumors. To determine whether rare meningioma variants carry NF2 mutations we analyzed 80 tumors. NF2 mutations were detected in 5 (36%) of 14 psammomatous, 1 (11%) of 9 angiomatous, 2 (22%) of 9 clear cell, 1 (33%) of 3 chordoid and 1 (100%) of 1 papillary meningioma. In the single papillary meningioma, 2 different NF2 mutations were observed. No NF2 mutations were found in 33 secretory, 7 microcystic, 2 lymphoplasmacyte-rich, one rhabdoid and one metaplastic meningioma. In the control group of 25 fibroblastic meningiomas, 11 cases were identified to carry an NF2 mutation. These results support the concept of different molecular subgroups of meningiomas which overlap with histological variants.

Primary clear cell meningioma of the orbit mimicking a metastatic carcinoma: usefulness of immunohistochemistry and cytogenetic analysis

“…Although loss or structural rearrangement of chromosome 22 has been largely described in typical meningiomas, the cytogenetic finding of CCM has not been reported to date [12,19,20,23]. Recently, Hartmann et al [6] reported 22% NF2 mutations in CCMs by single-strand conformational polymorphism.…”

Intracranial meningiomas in individuals under the age of 30; Analysis of risk factors, histopathology, and recurrence rate

“…Patients with the Wishart variant of NF2 may be at even greater risk of developing a meningioma and do so at an earlier age [6]. Meningiomas seen in association with NF2 have a propensity to arise from the optic nerve sheath and within the spinal canal and are more frequently multiple [9,24]. Loss of NF2 gene expression is ubiquitous in NF2 patients with meningiomas, while this is seen in 40-60% of all sporadic meningiomas.…”

“…Loss of NF2 gene expression is ubiquitous in NF2 patients with meningiomas, while this is seen in 40-60% of all sporadic meningiomas. It is possible that this genetic change may play a crucial role in meningioma formation, even in the absence of the NF2 syndrome [9,22,24,[36][37][38]. None of the patients in this study had any predisposing genetic syndrome or genetic factors.…”

Identification of a progenitor cell of origin capable of generating diverse meningioma histological subtypes

“…The central role of the NF2 gene in regulating leptomeningeal cell proliferation is underscored by the finding of biallelic NF2 gene inactivation in 50-80% of sporadic meningiomas (Ruttledge et al, 1994;Gutmann et al, 1997). In particular, NF2 loss is most frequently observed in the fibroblastic histological subtype (Hartmann et al, 2006).…”